DESCRIPTION: (Applicant's Description) Angiogenesis, formation of new blood vessels, is essential for progressive tumor growth and metastasis. Therapies aimed at inhibiting tumor angiogenesis (and shrinking tumors through nutrient starvation) hold great promise in cancer treatment, because they avoid two of the major problems associated with standard chemotherapy, i.e., the eventual growth of chemotherapy-resistant tumors and the debilitating systemic side effects engendered by chemotherapy. In particular, the rational design of biological agents that specifically suppress the angiogenic activity of tumor-promoting factors in the body is potentially an excellent means of creating such novel therapeutic agents. The specific aims of phase I of this proposal are 1) to generate and purify likely candidate biological agents that may specifically suppress the tumor angiogenic and tumor promoting activities of a particular angiogenic factor that is strongly implicated as an essential regulator of tumor growth, and 2) to screen these agents in a live animal model for their ability to block the angiogenic activity of the targeted factor. Agents identified as suppressors of the targeted factor's angiogenic activity would be tested in Phase II for their ability to suppress and/or regress the tumor growth-promoting activity of the targeted factor, and those that are able to do so would be developed further as clinical anti-cancer agents. PROPOSED COMMERCIAL APPLICATION: Cancer is the second leading cause of mortality in the U.S., and its health care costs are well over $100 billion. Solid tumors comprise the majority of cancers, afflict over 3 million people, and cause over a half million deaths annually. The health care market for anti- angiogenesis anti-cancer agents is very significant because conventional chemotherapy selects for resistant cancer cells, and causes significant toxicity to normal tissue.